This proposal is a competitive renewal of R01NS045879 "Stroke Imaging of Conscious Rats." In the previous grant cycle, we reported over two dozen peer-reviewed publications and leveraged multiple foundation grants to expand stroke research. Stroke remains to be the third leading cause of death and the leading cause of long-term disability. Our previous goals were to establish a rat stroke model with reproducible perfusion-diffusion mismatch (which approximates the ischemic penumbra), and to develop and apply quantitative perfusion, diffusion MRI and analysis methods to characterize pixel-by-pixel the spatiotemporal progression of diffusion and perfusion characteristics under different middle cerebral artery occlusion (MCAO) durations in the acute phase. Imaging measures were compared with histology. Gratifying progress was made on all previously proposed aims. In this competitive renewal, we seek to develop novel multimodal MRI approaches to probe the "physiological" and "functional" characteristics of the ischemic tissue at risk in stroke rats. These studies will focus on using blood-oxygenation-level dependent (BOLD) and cerebral blood flow (CBF) fMRI of physiologic (hypercapnic and oxygen) challenge and functional (stimulation and resting state) activity to probe perfusion and diffusion abnormality at 7 Tesla. We aim to apply these methodologies to study both acute and chronic stroke. Together, through an artificial neural-network predictive model, we will examine different MRI measures to accurately predict acute infarction and chronic recovery. Our central hypothesis is - through improved understanding of the physiological and functional profiles of ischemic tissue at risk and their spatiotemporal characteristics - tissue viability and functional recovery can be accurately predicted using only acute MRI data. PUBLIC HEALTH RELEVANCE: This proposal aims to develop novel multimodal MRI approaches to probe the "physiological" and "functional" characteristics of the ischemic tissue at risk in stroke rats. These non-invasive translational methodologies will provide a comprehensive anatomical, physiological and functional profile of ischemic tissue at risk and their spatiotemporal characteristics in a reproducible rat stroke model. These findings have the potential to positively impact stroke research, including testing of novel therapeutic strategies, as well as enhance clinical decision making in the treatment of acute stroke.